Innovative Clinical Trial Designs in NHLBI Related Research Areas – Meeting at ASH

Presentation copy from November 30, 2018 Meeting at ASH



Innovative trial designs are an array of techniques that improve the efficiency of clinical trials, either by reducing the resources required to answer a particular scientific question, or by enriching the quality of the answer the clinical trial provides. Flexible sample sizes, for example, fulfill the former attribute by directly reducing the sample size required in a trial, while an enrichment trial focuses on the latter attribute by providing additional information regarding subsets of the populations where patients are most likely to benefit from a novel treatment.

All innovative trial designs, by definition, have one or more features not present in a standard trial, defining a standard trial as the typical blinded 2 arm, 1:1 randomized, fixed sample size and population trial that has been the gold standard for clinical research for decades. Each feature of the standard trial exists to create robust, bias free inferences about the question of interest, often at great cost in time and resources. Innovative trial designs seek to maintain quality inferences while either decreasing the cost of the trial or increasing the scientific information gained in specific areas. For example, a noninnovative 5 arm trial would require large investment in all 5 arms. If 2-3 arms perform poorly early in a trial, removing these arms and reallocating those resources toward the remaining arms deviates from a standard fixed trial and produces a desirable tradeoff. We learn less about less promising arms, but more about arms more likely to be clinically valuable.

In evaluating and choosing potential trial designs, we must weigh whatever is lost in deviating from a standard trial to what is gained by performing the innovation. In this course we will quickly review the elements of the standard randomized clinical paradigm and note how each element arose to facilitate robust scientific conclusions, but often at high resource costs. These costs have rendered some forms of scientific inquiry, for example in hematological rare diseases, difficult to pursue in the traditional paradigm. We will then discuss multiple innovative trial methodologies, illustrating the tradeoffs that ensue.

Students completing the course will become familiar with a wide array of innovative trial techniques and the motivations and costs of pursuing each. Suggested attendees for this introductory learning event including hematologists and clinicians at all levels with and without clinical trial experience and with and without prior training in clinical trial design or statistical analysis This course is part of the NHLBI Innovative Clinical Trials Resource (ICTR), which will also provide a series of webinars and short videos on innovative trials that will be available to students as both preparation and allow for further study.

Instructors : Kert Viele, PhD and Anna McGlothlin, PhD

Kert Viele is a Director and Senior Statistical Scientist with Berry Consultants, with expertise in multiple innovative trial designs. He was previously at the University of Kentucky, where he won the Provost’s Award for Outstanding Teaching. He has taught short courses on innovative trial design, adaptive trial design, simulation, and Markov Chain Monte Carlo to academic, government, and industry audiences. Anna McGlothlin is a Senior Statistical Scientist at Berry Consultants. She also has extensive experience in innovative trial design and has taught design and simulation to industrial audience as well as an invited course in simulation to the FDA.